Adam M. Persky

Protective effect of estrogens against oxidative damage to heart and skeletal muscle in vivo and in vitro.

Estrogen has been shown to protect skeletal muscle from damage and to exert antioxidant properties. The purpose of the present study was to investigate the antioxidant and protective properties of estrogens in rodent cardiac and skeletal muscle and H9c2 cells. Female Sprague-Dawley rats were separated into three groups, ovariectomized (OVX), ovariectomized with estrogen replacement (OVX + E2), and intact control (SHAM), and were assessed at two time periods, 4 and 8 weeks. Rodents hearts were analyzed for basal and iron-stimulated lipid peroxidation in the absence and presence of beta-estradiol (betaE2) by measuring thiobarbituric acid reactive species (TBARS). Isolated soleus (SOL) and extensor digitorum longus (EDL) were analyzed for creatine kinase (CK) efflux. Using H9c2 cells, the in vitro effects of betaE2 and its isomer alpha-estradiol were investigated under glucose-free/hypoxic conditions. TBARS assay was also performed on the H9c2 in the presence or absence of betaE2. The results indicate that OVX rodent hearts are more susceptible to lipid peroxidation than OVX + E2 hearts. OVX soleus showed higher cumulative efflux of CK than OVX + E2. Furthermore, H9c2 survival during oxidative stress was enhanced when estrogen was present, and both OVX hearts at 4 weeks and H9c2 cells particularly were protected from oxidative damage by estrogens. We conclude that estrogen protects both skeletal and cardiac muscle from damage, and its antioxidant activity can contribute to this protection.

Pharmacokinetics of the Dietary Supplement Creatine

Creatine is a nonessential dietary component that, when supplemented in the diet, has shown physiological benefits in athletes, in animal-based models of disease and in patients with various muscle, neurological and neuromuscular disease. The clinical relevance of creatine supplementation is based primarily on its role in ATP generation, and cells may be able to better handle rapidly changing energy demands with supplementation.Although the pharmacological outcome measures of creatine have been investigated, the behaviour of creatine in the blood and muscle is still not fully understood. Creatine is most probably actively absorbed from the gastrointestinal tract in a similar way to amino acids and peptides. The distribution of creatine throughout the body is largely determined by the presence of creatine transporters. These transporters not only serve to distribute creatine but serve as a clearance mechanism because of creatine ‘trapping’ by skeletal muscle. Besides the pseudo-irreversible uptake by skeletal muscle, creatine clearance also depends on renal elimination and degradation to creatinine.Evidence suggests that creatine pharmacokinetics are nonlinear with respect to dose size and frequency. Skeletal muscle, the largest depot of creatine, has a finite capacity to store creatine. As such, when these stores are saturated, both volume of distribution and clearance can decrease, thus leading to complex pharmacokinetic situations. Additionally, other dietary components such as caffeine and carbohydrate can potentially affect pharmacokinetics by their influence on the creatine transporter. Disease and age may also affect the pharmacokinetics, but more information is needed.Overall, there are very limited pharmacokinetic data available for creatine, and further studies are needed to define absorption characteristics, clearance kinetics and the effect of multiple doses. Additionally, the relationship between plasma creatine and muscle creatine needs to be elucidated to optimise administration regimens.

The impact of team-based learning on a foundational pharmacokinetics course.

Objective. To assess the impact of team-based learning (TBL) in a foundational pharmacokinetics course. Design. The course was arranged into 5 modules based on the TBL format. Each module contained preclass preparation; readiness-assurance process; and in-class, clinical cases. Survey instruments on professionalism and attitudes of team learning were administered pre- and post-course. Assessment. Examination grades focused at the evaluation/creation level were significantly higher in the TBL format compared with the previous year. Professionalism scores increased over the course of the semester, particularly in altruism and honesty. Other measures of team-learning attitudes significantly increased over time, although there was no change in major subscales. End-of-semester course evaluations showed improvements in active engagement and in various areas of skill development. Conclusion. The TBL format can be used successfully in a foundational pharmacokinetics course to increase higher levels of learning, team-learning skills, and professionalism in pharmacy students.

Single‐ and Multiple‐Dose Pharmacokinetics of Oral Creatine

Supplementation with exogenous creatine (Cr) has shown physiological benefits in humans, but little is known about the pharmacokinetics of Cr in humans. Six healthy males completed an open‐label study consisting of a full pharmacokinetic analysis following a single oral dose of Cr monohydrate (71 mg kg−1) and at steady‐state after 6 days of Cr administration (71 mg kg−1 qid). After the single oral dose, the clearance (CL/F) was 0.20 ± 0.066 L h−1 kg−1, tmax was 1.9 ± 0.88 hours, and Cmax = 102.1 ± 11.2 mg h L−1. At steady‐state, CL/F decreased to 0.12 ± 0.016 L h−1 kg−1, tmax did not change, and Cmax increased to 162.2 ± 30.0 mg L−1. Penetration (AUCMUSCLE/AUCPLASMA) of Cr into the interstitial muscle space, as determined by microdialysis, was 0.47 ± 0.09 and 0.37 ± 0.27 for the single dose and at steady‐state, respectively. Plasma and muscle data were simultaneously fitted with a model incorporating a saturable absorption and first‐order elimination process. In conclusion, repeated dosing of Cr caused a reduction in clearance that could result from saturation of the skeletal muscle pool of Cr.

Safety of Creatine Supplementation

The literature on creatine supplementation supporting its efficacy has grown rapidly and has included studies in both healthy volunteers and patient populations. However, the first rule in the development of therapeutic agents is safety. Creatine is well-tolerated in most individuals in short-term studies. However, isolated reports suggest creatine may be associated with various side effects affecting several organ systems including skeletal muscle, the kidney and the gastrointestinal tract. The majority of clinical studies fail to find an increased incidence of side effects with creatine supplementation. To date, studies have not found clinically significant deviations from normal values in renal, hepatic, cardiac or muscle function. Few data are available on the long-term consequences of creatine supplementation.

A Modified Team-Based Learning Physiology Course

Objective. To implement and assess an interactive, clinically applicable first-year physiology course using team-based learning. Design. The course was designed on a team-based learning backbone using 6 modules, pre-class preparation, a readiness-assurance process, and in-class application. Integrative cases were used to review concepts prior to examinations. Various assessment methods were used to measure changes, including course evaluations, an attitudinal survey tool, and a knowledge examination. Assessment. Course evaluations indicated a higher perception of active learning in the revised format compared with that of the previous years course format. There also were notable differences in opportunities to promote communication skills, work as part of a team, and collaborate with diverse individuals. The assessment of content knowledge indicated that students who completed the revised format course outperformed the previous years students in both foundational knowledge and application-type questions. Conclusion. Using more team-based learning within a physiology course had a favorable impact on student retention of material and attitudes toward the course.

Best Practices for Implementing Team-Based Learning in Pharmacy Education

Colleges and schools of pharmacy are incorporating more team-based learning (TBL) into their curriculum. Published resources are available to assist instructors with implementing TBL and describing it in the health professions literature. The 7 core elements include: team formation, readiness assurance, immediate feedback, sequencing of in-class problem solving, the 4 “S” structure for developing team application exercises (significant problem, same problem, specific answer choice, simultaneous reporting), incentive structure, and peer evaluation. This paper summarizes best practices related to implementation of TBL in pharmacy education, including courses taught using teaching teams.

Effects of repeated creatine supplementation on muscle, plasma, and urine creatine levels.

The purpose of this case study was to examine the effects of repeated creatine administration on muscle phosphocreatine, plasma creatine, and urine creatine. One male subject (age, 32 years; body mass, 78.4 kg; height, 160 cm; resistance training experience, 15 years) ingested creatine (20 g-d-1 for 5 days) during 2 bouts separated by a 30-day washout period. Muscle phosphocreatine was measured before and after supplementation. On day 1 of supplementation, blood samples were taken immediately before and hourly for 5 hours following ingestion of 5 g of creatine, and a pharmacokinetic analysis of plasma creatine was conducted. Twenty-four-hour urine collections were conducted before and for 5 days during supplementation. Muscle phosphocreatine increased 45% following the first supplementation bout, decreased 22% during the 30-day washout period, and increased 25% following the second bout. There were no meaningful differences in plasma creatine pharmacokinetic parameters between bouts 1 and 2. Total urine creatine losses during supplementation were 63.2 and 63.4 g during bouts 1 and 2, respectively. The major findings were that (a) a 30-day washout period is insufficient time for muscle phosphocreatine to return to baseline following creatine supplementation but is sufficient time for plasma and urine creatine levels to return to presupplementation values; (b) postsupplementation muscle phosphocreatine levels were similar following bouts 1 and 2 despite 23% higher presupplementation muscle phosphocreatine before bout 2; and (c) the increased muscle phosphocreatine that persisted throughout the 30-day washout period corresponded with maintenance of increased body mass ( + 2.0 kg). Athletes should be aware that the washout period for muscle creatine to return to baseline levels may be longer than 30 days in some individuals, and this may be accompanied by a persistent increase in body mass.

Validation of a simple liquid chromatography assay for creatine suitable for pharmacokinetic applications, determination of plasma protein binding and verification of percent labeled claim of various creatine products

Creatine has been quantified in various tissues by a range of methodologies. This paper reports on the development and validation of a simplified HPLC assay to determine plasma creatine, plasma protein binding of creatine, creatine in microdialysate and creatine in over-the-counter products. An isocratic, reversed-phase (C(18)) HPLC assay, using potassium phosphate monobasic (pH 4) as a mobile phase, was validated in human plasma and microdialysis perfusion fluid (normal saline). The lower limit of quantification for the assay was 1 mg l(-1) in saline and 5 mg l(-1) in plasma. The RSD was below 6% and accuracy was below 12% in both matrices. Protein binding in human plasma was found to be negligible (<10%). Over-the-counter creatine monohydrate products tested contained 100% creatine monohydrate. This assay was found to be suitable for pharmacokinetic studies and the assessment of plasma creatine and skeletal muscle microdialysate.

Correlation of the Health Sciences Reasoning Test With Student Admission Variables

Objectives. To assess the association between scores on the Health Sciences Reasoning Test (HSRT) and pharmacy student admission variables. Methods. During the student admissions process, cognitive data, including undergraduate grade point average and Pharmacy College Admission Test (PCAT) scores, were collected from matriculating doctor of pharmacy (PharmD) students. Between 2007 and 2009, the HSRT was administered to 329 first-year PharmD students. Correlations between HSRT scores and cognitive data, previous degree, and gender were examined. Results. After controlling for other predictors, 3 variables were significantly associated with HSRT scores: percentile rank on the reading comprehension (p<0.001), verbal (p<0.001), and quantitative (p<0.001) subsections of the PCAT. Conclusions. Scores on the reading comprehension, verbal, and quantitative sections of the PCAT were significantly associated with HSRT scores. Some elements of critical thinking may be measured by these PCAT subsections. However, the HSRT offers information absent in standard cognitive admission criteria.